Rate of seroconversion for routine vaccinations in patients with chronic lymphocytic leukemia on ibrutinib.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19509-e19509
Author(s):  
Mohammad Ammad Ud Din ◽  
Saad Jamshed
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Kinase Inhibitors ◽  
De Novo ◽  
Seroconversion Rate ◽  
Geometric Mean ◽  
Humoral Response ◽  
Lymphocytic Leukemia ◽  
Post Vaccination ◽  
Bruton Tyrosine Kinase ◽  
Anti Cd20

e19509 Background: It is unclear whether Bruton tyrosine kinase inhibitors (BTKi) contribute to the humoral dysfunction in chronic lymphocytic leukemia. Methods: A literature search of PubMed, EmCare, and Google Scholar was performed on December 5, 2020. Five studies met inclusion criteria out of 249 studies per PRISMA guidelines (n = 244). Results: Pleyer et al. and Zent et al. showed an adequate recall humoral response to the shingle vaccine (41.5% and 75% seroconversion rate respectively), however, de novo response to hepatitis B vaccine was greatly reduced. Conflicting results were seen for the influenza vaccine as Sun et al. showed a significant increase in post-vaccination geometric mean titers for all three strains while only 7% of patients demonstrated seroconversion in the study by Douglas et al. None of the patients responded to the pneumococcal conjugate vaccine in a study by Andrick et al, though the results were not statistically significant (p = 0.029) (Table). Conclusions: Treatment with BTKi may not cause significant detrimental response to immunization but further studies are needed to elucidate longterm effects especially in patients with prior exposure to anti-CD20 antibodies.[Table: see text]

An update of venetoclax and obinutuzumab in chronic lymphocytic leukemia

2020 ◽  
Author(s):  
Ross Salvaris ◽  
Stephen Opat
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Kinase Inhibitors ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Novel Agents ◽  
Bruton Tyrosine Kinase ◽  
Phase Iii Trials ◽  
Treatment Naïve ◽  
Cd20 Antibody ◽  
Anti Cd20

In the last decade, the treatment of chronic lymphocytic leukemia (CLL) has shifted away from chemoimmunotherapy toward targeted novel agents such as small molecule inhibitors and antibodies. Here, we give an overview of the pharmacology of venetoclax and obinutuzumab and the evidence from early phase to Phase III trials that have shaped how they are used in the treatment of CLL. Venetoclax, an oral anti-apoptotic BCL-2 inhibitor, in combination with a CD20 antibody has shown superiority to chemoimmunotherapy in treatment-naive and relapsed/refractory CLL. Obinutuzumab is a novel anti-CD20 monoclonal antibody that has been safely combined with novel agents including venetoclax and Bruton tyrosine kinase inhibitors and has shown superiority over rituximab when combined with chlorambucil.

scholarly journals Standard treatment approaches for relapsed/refractory chronic lymphocytic leukemia after frontline chemoimmunotherapy

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 33-40
Author(s):  
Carol Moreno
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Kinase Inhibitors ◽  
Cellular Therapy ◽  
Negative Impact ◽  
Lymphocytic Leukemia ◽  
Cell Transplant ◽  
Phosphatidylinositol 3 Kinase ◽  
Bruton Tyrosine Kinase ◽  
Therapy Treatment

Abstract Despite the effectiveness of chemoimmunotherapy (CIT), in most cases the clinical course of chronic lymphocytic leukemia (CLL) is characterized by consecutive episodes of disease progression and need for therapy. Treatment possibilities for patients with CLL in whom CIT fails whose disease progresses after initial CIT include pathway inhibitors (PIs) and, for selected patients, cellular therapy (ie, allogeneic stem cell transplant, chimeric antigen receptor T cells). PIs (ie, Bruton tyrosine kinase inhibitors, phosphatidylinositol 3-kinase inhibitors, and BCL2 inhibitors) are revolutionizing the treatment of CLL. PIs have proved to be more effective than CIT, both as upfront therapy and for relapsed/refractory disease, largely because they may overcome the negative impact of adverse biomarkers (eg, TP53 aberrations, unmutated IGHV) on outcomes and because of their acceptable toxicity. In this article, the management of patients with relapsed/refractory CLL is discussed, with a particular emphasis on the role of PIs.

scholarly journals Safety and efficacy of BNT162b mRNA Covid19 Vaccine in patients with chronic lymphocytic leukemia

Haematologica ◽  
2021 ◽  
Author(s):  
Ohad Benjamini ◽  
Lior Rokach ◽  
Gilad Itchaki ◽  
Andrei Braester ◽  
Lev Shvidel ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Humoral Response ◽  
Lymphocytic Leukemia ◽  
Safety And Efficacy ◽  
Patient Will ◽  
Treatment Naïve ◽  
High Concordance ◽  
Anti Cd20

Patients with chronic lymphocytic leukemia (CLL) have a suboptimal humoral response to vaccination. Recently, a BNT162b2 mRNA COVID-19 vaccine was introduced with a high efficacy of 95% in immunocompetent individuals. We investigated the safety and efficacy of BNT162b2 mRNA Covid-19 vaccine in patients with CLL from nine medical centers in Israel, In total 400 patients were included, of which 373 were found to be eligible for the analysis of antibody response. The vaccine appeared to be safe and only grade 1-2 adverse events were seen in 50% of the patients. Following the second dose, antibody response was detected in 43% of the cohort. In treatment- naïve patients 61% responded to the vaccine, while only 18%, 37% and 5% of patients with CLL ongoing, previously treated with BTKi, or recent anti CD20 antibody developed responses respectively. 62% and 14% of patients treated with BCL2 monotherapy or combined with anti CD20 developed immune response respectively. Neutralizing antibodies demonstrated high concordance with positive serologic response to spike (S) protein. Based on our results a simple scoring model including recent treatment with anti-CD20, age younger than 70 years, treatment naïve status, and normal IGG, IGA, IGM and hemoglobin levels. The sum of all the above parameters can serve as a possible estimate to predict whether a given CLL patient will develop sufficient antibodies. In conclusion, the vaccine was found to be safe in patients with CLL, but its efficacy is limited particularly in treated patients.

Acute gout flare of bilateral first metatarsophalangeal joints due to ibrutinib use in chronic lymphocytic leukemia

2021 ◽  
pp. 107815522110297
Author(s):  
Jaspreet Kaur ◽  
Shahaf Tuler ◽  
Constantin A Dasanu
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Kinase Inhibitors ◽  
Oxidase Inhibitor ◽  
Lymphocytic Leukemia ◽  
Acute Gout ◽  
Xanthine Oxidase Inhibitor ◽  
Bruton Tyrosine Kinase ◽  
Metatarsophalangeal Joints ◽  
Mtp Joints ◽  
Gout Flare

Introduction Bruton tyrosine kinase inhibitors represent important tools in the therapeutic armamentarium against chronic lymphocytic leukemia (CLL) and other B-lymphoproliferative disorders. Case Report We describe herein a unique 65-year-old patient who presented with bilateral foot pain four months after starting treatment with ibrutinib for CLL. Of note, the patient had previously been diagnosed with gout, and was taking allopurinol prophylactically at the time of the event. Compliance with allopurinol was in excess of 99%. Yet, he was diagnosed with acute gout flare of bilateral first metatarsophalangeal (MTP) joints. Management & Outcome: Ibrutinib dose was reduced by one third, and the patient’s gout flare up was treated with ibuprofen as needed. After symptoms abated, ibrutinib was continued at 2/3rds of the dose, with an excellent CLL control. The patient tolerated this dose without any further adverse effects. Discussion/Conclusions: We have reported a unique side effect of acute bilateral first MTP joint gout flare likely triggered by ibrutinib use for CLL while the patient was taking a xanthine oxidase inhibitor. The mechanism by which ibrutinib caused this phenomenon remains to be elucidated.

scholarly journals The role of second generation Bruton tyrosine kinase inhibitors in the treatment of chronic lymphocytic leukemia. Resolution

2020 ◽  
Vol 21 (4) ◽  
pp. 45-47
Author(s):  
Irina V. Poddubnaya ◽  
Tatyana E. Bialik ◽  
Natalya N. Glonina ◽  
Olga B. Kalashnikova ◽  
Kamil D. Kaplanov ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Important Place ◽  
First Line Therapy ◽  
Line Therapy ◽  
Bruton Tyrosine Kinase ◽  
Adult Leukemia

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, with incidence rate of 4: 100 thousand per year, according to European data. CLL remains an incurable disease, with most patients over 60 years old. Immunochemotherapy schemes today remain the standard treatment approach for CLL. The advent of novel molecules expands possibilities of treating this disease. Targeted therapy with small molecule inhibitors of Bruton tyrosine kinase (BTK) occupies an important place in the treatment of patients with CLL, both for first-line therapy and for treatment of relapses. The drug acalabrutinib as a highly selective new generation of BTK inhibitor can be considered as an efficient and safe option for first-line therapy and for treatment of the disease relapse in patients with CLL, especially in patients with comorbidity, including cardiovascular diseases (CDV) or risk factors for CVD.

scholarly journals Humoral response to mRNA anti-COVID-19 vaccines BNT162b2 and mRNA-1273 in patients with chronic lymphocytic leukemia

2021 ◽  
Author(s):  
Cristina Bagacean ◽  
Rémi Letestu ◽  
Chadi Al-Nawakil ◽  
Ségolène Brichler ◽  
Vincent Lévy ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Chronic Lymphocytic Leukemia ◽  
Immune Responses ◽  
Response Rate ◽  
Humoral Response ◽  
Lymphocytic Leukemia ◽  
Post Dose ◽  
Treatment Naïve ◽  
Previously Treated ◽  
Anti Cd20

Immunocompromised individuals such as chronic lymphocytic leukemia (CLL) patients are at risk of impaired immune responses to vaccination. The objective of our study was to evaluate SARS-CoV-2-specific antibody responses in CLL patients, after the first, second and third doses of the BNT162b2 and mRNA-1273, and after a single dose for patients with confirmed prior COVID-19. Five hundred and thirty patients were included in the study. Patients received 2 doses at a 4-week interval, and a third dose if seronegative after the second dose. Response rate was 27% post-dose 1 and 52% post-dose 2. Post-dose 2 treatment-naïve patients had the highest response rate (72%) followed by patients previously treated by chemoimmunotherapy (60%). Among patients on therapy, patients on BTKi alone (22%) or in combination with anti-CD20 monoclonal antibodies or venetoclax (0%) had the poorer response rate whereas patients on venetoclax monotherapy achieved a significantly higher response rate (52%). A multivariate analysis identified as independent predictors of the absence of seroconversion: age >65 years, ongoing CLL treatment and gamma-globulins ≤6g/L. Post-dose 2 seronegative patients had a global post-dose 3 response rate of 35%. This study provides an argument for the use of a third dose and for prophylactic SARS-CoV-2 neutralizing monoclonal antibodies.

Bruton tyrosine kinase inhibitors for chronic lymphocytic leukemia

2021 ◽  
Vol 2021 (9) ◽  
Author(s):  
Jacob Schmelz ◽  
Philip Heesen ◽  
Anish Patnaik ◽  
Travis Holder ◽  
Hun J Lee ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Lymphocytic Leukemia ◽  
Bruton Tyrosine Kinase
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